IL-6 is a glycoprotein with a molecular weight of 21,000 that is produced from T cells, macrophages, fibroblasts, muscular cells and the like when stimulated with a mitogen, viral infection, or IL-1. Human IL-6 consists of 184 amino acids and its gene is present on the 7th chromosome. IL-6 has diverse biological activities including (1) induction of cellular proliferation (hybridomas, T cells, keratinocytes, renal mesangial cells), (2) inhibition of cellular proliferation (myelogenic leukemia cell lines, malignant melanoma cell lines), and (3) induction of cellular differentiation and induction of production of cellular specific proteins (neural differentiation of melanocytoma cell lines, differentiation of killer T cells, maturation of megakaryocytes, differentiation into macrophages of myelogenic leukemia cell lines, antibody production of B cells, production of acute phase proteins in hepatocytes). Due to its diverse biological activities, it has been indicated that IL-6 may be relevant to some diseases. In recent years, it is known that IL-6 is involved in onset of diseases including (1) rheumatoid arthritis, atrial myxoma, Castleman disease, hypergammaglobulinemia or autoimmune symptoms in AIDS, (2) mesangial nephritis, (3) psoriasis, and (4) Kaposi sarcoma in AIDS. Recently, it is also known that a large quantity of IL-6 is produced from the skeletal muscle immediately after physical practice, which stimulates hypothalamus to secrete various neurohormones to thereby affect the immune system (Dictionary of Immunology, 1st ed., p. 49, 1993).
Among the diseases where IL-6 is involved, rheumatoid arthritis (RA) afflicts about 7×105 people all over the country in Japan with gradual increase and together with increase in the number of aged patients is becoming a social problem (Ogata A. et al., Rinsho Byori (Clinical Pathology), 1999 April; 47 (4): 321-326 [Advances in interleukin-6 therapy]).
The cause of RA is not known. RA, an autoimmune disease wherein an autoimmune reaction within the articular cavity has continued and became chronic, is assigned as one of inveterate specific diseases. Relevancy of RA to IL-6 has been investigated to reveal that a large quantity of IL-6 is present in joint fluid from RA patients and that IL-6 is involved not only in induction of inflammation but also in proliferation of fibroblasts in the synovial membrane. There is also possibility that IL-6 may accelerate production of autoantibody (Nishimoto N. et al., Clinical application of interleukin-6 receptor antibody, transactions of Japanese Society for Immunology 1997; 20: 87-94).
Accordingly, anti-IL-6 antibody that inhibits the biological activities of IL-6 would be a candidate of a nosotropic medicament for treating several immunopathies including RA and is practically under investigation (Mihara M. et al., Br. J. Rheumatol. 1995 April; 34(4): 321-325; Mihara M. et al., Clin. Immunol. 2001, 98: 319-326).